FIGURE 5 from Epigenetic Priming by Hypomethylation Enhances the Immunogenic Potential of Tolinapant in T-cell Lymphoma

Pharmacodynamic changes in ICD biomarkers, chemokines/cytokines, and gene expression in models of TCL in vivo and in patients. A, Western blots of tumor lysates from a BW5147 tumors grown in wild-type mice. Tumor-bearing animals were treated with five daily doses of each compound alone or in combination then culled 2 hours after the final dose. B, Changes (log₂ fold change relative to vehicle control) in a panel of 43 chemokine/cytokines measured by Luminex assay in plasma of the treated animals. C, Protein analysis by Western blots and of lysates from Karpas-299 tumors in CB17 SCID mice. Tumors were taken after three daily doses of each compound alone or in combination. D, Relative expression by qPCR analysis from RNA extracted from tumors taken after three daily doses of compounds as described in C. Signal for each gene was normalized to the level of 18S housekeeping as control. * Indicates an estimation of relative expression because this gene was not detected in vehicle control (vehicle control CT set to 40). E, Histogram showing relative change in IP-10 levels. The data are represented as log₂ fold change in PTCL patient (n = 63 patients) between early times in C1 and late times in cycle C1. “Early” refers to pretreatment and 2 hours posttreatment samples; “late” refers to mostly day 2 (after the first dose), day 7, and day 8 at the end of 7 daily doses in C1. F, Longitudinal data showing relative plasma IP-10 levels in patients during the first two cycles. C1 (as described above) pattern was repeated during cycle 2 (C2). Cycle 2 was initiated 7 days after the last tolinapant administration. P values from binomial one-tailed test.